Regulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86146
Title:
Regulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2.
Authors:
Pye, David A; Vivès, Romain R; Hyde, Patricia; Gallagher, John T
Abstract:
The interaction of heparan sulfate (HS) (and the closely related molecule heparin) with FGF-1 is a requirement for enabling the growth factor to activate its cell surface tyrosine kinase receptor. However, little is known about the regulatory role of naturally occurring cell surface HS in FGF-1 activation. We have addressed this issue by utilizing a library of HS oligosaccharides, which are defined in both length and sulfate content. Mitogenic activation assays using these oligosaccharides showed that HS contained both FGF-1 activatory and inhibitory sugar sequences. Further analysis of these oligosaccharides showed a clear correlation between FGF-1 promoting activity and their 6-O-sulfate content. The results, in particular with the dodecasaccharide sequences, suggested that specific positioning of 6-O-sulfate groups may be required for the promotion of FGF-1 mitogenic activity. This may also be true for 2-O-sulfate groups though the evidence was not as conclusive. Differential activation of FGF-1 and FGF-2 was also observed and found to be mediated by both oligosaccharide length and sulfation pattern, with different specific O-sulfate positioning being implicated for the promotion of different growth factors. These results suggest that variation and tight control of the fine structure of HS may allow cells to not only control their positive/negative responses to individual FGFs but also to change specificity towards promotion of different members of the FGF family.
Affiliation:
CRC Department of Drug Development and CRC and University of Manchester Department of Medical Oncology, PICR, Christie Hospital, Manchester M20 4BX, UK.
Citation:
Regulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2. 2000, 10 (11):1183-92 Glycobiology
Journal:
Glycobiology
Issue Date:
Nov-2000
URI:
http://hdl.handle.net/10541/86146
DOI:
10.1093/glycob/10.11.1183
PubMed ID:
11087710
Type:
Article
Language:
en
ISSN:
0959-6658
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPye, David Aen
dc.contributor.authorVivès, Romain Ren
dc.contributor.authorHyde, Patriciaen
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2009-11-13T15:11:51Z-
dc.date.available2009-11-13T15:11:51Z-
dc.date.issued2000-11-
dc.identifier.citationRegulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2. 2000, 10 (11):1183-92 Glycobiologyen
dc.identifier.issn0959-6658-
dc.identifier.pmid11087710-
dc.identifier.doi10.1093/glycob/10.11.1183-
dc.identifier.urihttp://hdl.handle.net/10541/86146-
dc.description.abstractThe interaction of heparan sulfate (HS) (and the closely related molecule heparin) with FGF-1 is a requirement for enabling the growth factor to activate its cell surface tyrosine kinase receptor. However, little is known about the regulatory role of naturally occurring cell surface HS in FGF-1 activation. We have addressed this issue by utilizing a library of HS oligosaccharides, which are defined in both length and sulfate content. Mitogenic activation assays using these oligosaccharides showed that HS contained both FGF-1 activatory and inhibitory sugar sequences. Further analysis of these oligosaccharides showed a clear correlation between FGF-1 promoting activity and their 6-O-sulfate content. The results, in particular with the dodecasaccharide sequences, suggested that specific positioning of 6-O-sulfate groups may be required for the promotion of FGF-1 mitogenic activity. This may also be true for 2-O-sulfate groups though the evidence was not as conclusive. Differential activation of FGF-1 and FGF-2 was also observed and found to be mediated by both oligosaccharide length and sulfation pattern, with different specific O-sulfate positioning being implicated for the promotion of different growth factors. These results suggest that variation and tight control of the fine structure of HS may allow cells to not only control their positive/negative responses to individual FGFs but also to change specificity towards promotion of different members of the FGF family.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCarbohydrate Sequence-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshFibroblast Growth Factor 1-
dc.subject.meshFibroblast Growth Factor 2-
dc.subject.meshFibroblast Growth Factors-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshMice-
dc.subject.meshMitogens-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshOligosaccharides-
dc.subject.meshStructure-Activity Relationship-
dc.titleRegulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Drug Development and CRC and University of Manchester Department of Medical Oncology, PICR, Christie Hospital, Manchester M20 4BX, UK.en
dc.identifier.journalGlycobiologyen

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